Non-small-cell lung cancer: guideline history

Anchored to: FDA approval of first-line osimertinib, April 2018 (FLAURA)

• recategorisedMetastatic, EGFR-mutant, first line: Osimertinib becomes the preferred first-line EGFR TKI over erlotinib, gefitinib and afatinib.one of several first-line TKIs → preferred (category 1)

Anchored to: FDA approvals of adjuvant osimertinib (December 2020, ADAURA), sotorasib and amivantamab (May 2021), adjuvant atezolizumab (October 2021, IMpower010)

• addedAdjuvant, EGFR-mutant, stage IB-IIIA: Osimertinib for 3 years after resection and adjuvant chemotherapy.
• addedMetastatic, KRAS G12C, second line: Sotorasib after prior systemic therapy; adagrasib followed in December 2022.
• addedMetastatic, EGFR exon 20 insertion: Amivantamab after platinum chemotherapy.
• addedAdjuvant, stage II-IIIA, PD-L1 1% or above: Atezolizumab for one year after adjuvant chemotherapy.

Anchored to: Annals of Oncology publication, 2023

• addedMetastatic, ALK-positive, first line: Lorlatinib, alectinib or brigatinib recommended first line; crizotinib no longer preferred.
• addedMetastatic, KRAS G12C, second line: Sotorasib or adagrasib after first-line immunochemotherapy [III, A].

Anchored to: FDA approvals of neoadjuvant nivolumab with chemotherapy (March 2022, CheckMate 816) and perioperative pembrolizumab (October 2023, KEYNOTE-671)

• addedResectable stage II-IIIB, neoadjuvant: Nivolumab with platinum doublet for 3 cycles before surgery.
• addedResectable stage II-IIIB, perioperative: Pembrolizumab with platinum doublet before surgery and pembrolizumab alone after.

Anchored to: FDA approvals of osimertinib with chemotherapy (February 2024, FLAURA2), adjuvant alectinib (April 2024, ALINA), amivantamab with lazertinib (August 2024, MARIPOSA) and osimertinib after chemoradiation (September 2024, LAURA)

• addedMetastatic, EGFR-mutant, first line: Osimertinib plus pemetrexed-platinum and amivantamab plus lazertinib added alongside osimertinib alone.
• addedAdjuvant, ALK-positive, stage IB-IIIA: Alectinib for 2 years after resection.
• addedStage III unresectable, EGFR-mutant: Osimertinib after definitive chemoradiation until progression, in place of durvalumab.

Anchored to: FDA approval of datopotamab deruxtecan for EGFR-mutant NSCLC after TKI and chemotherapy (June 2025, TROPION-Lung05); withdrawal of the patritumab deruxtecan application (May 2025)

• addedMetastatic, EGFR-mutant, after TKI and chemotherapy: Datopotamab deruxtecan as a later-line option.
• removedMetastatic, EGFR-mutant, after TKI: Patritumab deruxtecan not added after the BLA was withdrawn following a CRL and the HERTHENA-Lung02 overall-survival miss.